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Saturday, June 16, 2012

Thin Endometrium –a side-effect of calorie restriction and fat loss?

Vaginal ultrasound showing a thin endometrium

I always had great endometrial lining during all my IVF cycles (greater than 8mm, mostly between 10-12 mm). In FET cycle too there was no problem. So, what went wrong this time? Even though I can just speculate, I know deep within me that my speculation is right. I have lost lots of weight during the past 5 months. I was insulin resistant before. I had a HOMA IR (a measure of insulin resistance) of 4.1. There is no standard value for HOMA-IR. The current studies consider that HOMA-IR < 2 is normal, HOMA-IR ≥ 2 is pathological, with HOMA-IR > 4 reflecting the pre-diabetic stage. My fasting insulin was 17uUnits/ml (although a fasting insulin of 5-25uUnits/ml is considered normal, anything above 10uUnits/ml is not so good. People with fasting insulin of less than 5uUnits/ml are found to live longer). I have a family history of diabetes in my dad’s side. I was diagnosed with PCOD at the age of 25 and I am on metformin (1500mg) for a long time. I stopped metformin for the past year because of gastrointestinal problem. After stopping metformin my BMI was 26.2. I was overweight. Lack of implantation in my previous ART cycle made me to ponder what can be done to improve my chance of conceiving. The only sore point I had is my weight and perhaps insulin resistance because of it. My blood glucose was normal. I also became aware of the fact that calorie restriction has a positive impact on egg quality. This made me to think seriously about removing the excess weight. My boss is an endocrinologist. I used to discuss with him about the weight issue and ask him whether carbohydrate rich meals are the culprit. He used to say-eat anything, but eat less. I started a very strict calorie restriction diet and jogging. I limited my calories to 800-1000 for the first 2 weeks. I achieved this by intermittent fasting. To my surprise my fat deposits around my waist started to melt. After two weeks I upped my calories to 1200-1500 calories. I avoided sugar, sweets and carbohydrate rich foods. I avoided rice as much as I can. I took only 300 calories per meal. I started metformin 1000mg. I stopped non-vegetarian all together and I am not planning to eat it anymore during my lifetime :). Within 5 months my weight dropped from 68 kg to 61 kg. The best point is I lost all the excess fat. For the first time I had a flat stomach. My energy levels improved. I can skip a meal easily without any trouble. I attribute it to my lowered insulin levels. In short I felt great. Received mixed comments from friends. Some are worried. They said I have lost the charm. But my DH is happy. He said I looked better now. I am happy too :)

Everything sounds good, right? Then, where lays the problem? Calorie restriction is good. It was found to prevent aging in experimental animals. It also delayed egg cell aging and extended fertility in experimental mice. Metformin is a calorie restriction mimetic too. It can also improve egg quality (both by preventing egg cell aging and by decreasing insulin levels). I do not think short time calorie restriction will have any effect on egg quality in humans. If calorie restriction is started in 20s it might extend fertility into your 40s. The same is true with metformin usage. Long term metformin intake can preserve egg quality via preventing genetic defect accumulation, while short term intake can increase egg quality by decreasing insulin levels. It was found that exercise and weight loss is much effective than metformin in decreasing insulin levels. So bringing down your weight at any point of your lifetime will have positive effect on your overall health by decreasing insulin, glucose and harmful triglyceride levels. This will keep your hormones balanced which is necessary for optimal fertility. As a result egg quality (not genetic but physiological parameters) and  endometrial health improves. Consider calorie restriction if you are suffering with infertility due to overweight and PCOD (high insulin!).  Reduce your weight through calorie restriction and proper exercise. Continue exercise regimen and increase your calorie intake for maintaining the appropriate weight. BUT never do calorie restriction when you are on fertility medicines, if you are underwieght or when you are trying to conceive.  Never be on very restricted calories (less than 1500 calories) when you are trying to conceive. This is the mistake I did this cycle. Even after starting fertility medicines (progynova) I continued with fewer calories. Lesser calories actually signal your body to go into the survival mode (during which only minimal bodily functions are maintained). Reproduction is an extremely energy consuming process. Once your body senses that you do not have enough calorie supply (as in times of food scarcity) it switches on mechanisms which  prevents energy expenditure. It tries to switch off high energy demanding functions like reproduction. In short all the anabolic activities which require high energy are switched off and catabolic processes which produce energy are switched on. Since I took less calories my estrous cycle is severely affected leading to poor endometrial development. My body in short doesn’t want to get ready for performing reproductive function.

I got this information from a website:

Reproduction: Feeding the reproductive cycle
Energy metabolism is known to affect reproductive cycles, acting as an evolutionary oversight to ensure that reproduction occurs only in favorable nutritional conditions. A recent study characterizes a mechanism through which the liver integrates metabolic responses to control ovulation (Cell Metab. 13, 205214).
Investigating the link between estrogen and food consumption in mice, Sara Della Torre and colleagues found that caloric restriction decreased hepatic estrogen receptor-α (ER-α) activation in the liver and arrested estrous cycle progression. Interestingly, amino acid supplementation was sufficient to rescue mice from this metabolic block of the estrous cycle.
The authors found that ER-α activation led to increased hepatic expression of insulin growth factor–like-1 (IGF-1) and increased the amount of circulating IGF-1. Increased IGF-1 expression was required for E2-induced proliferation of uterine lumen epithelial cells and for estrous cycle progression in vivo.
The findings highlight a crucial role of hepatic ER-α as an integrator of metabolic and reproductive functions. The exact mechanisms by which IGF-1 and E2 promote progression of the estrous cycle remain to be determined, but this study might provide insights into infertility conditions, especially those linked to metabolic dysfunction. 

On the other hand there must be a connection between fat reserve and estrogen function. It is known that estrogen is stored in fat reserves. I have read that people who are obese are prone to estrogen sensitive breast cancers. Overweight people are also more prone to endometrial cancer. You need healthy fat reserves for your estrogen to function properly. Dr.Malpani sent me the Frisch hypothesis paper which talks about the connection between body weight and onset of menarche.

In short I learned a lesson which is invaluable. Do not change your diet or exercise regimen extremely during IVF or FET cycles.  Do not loose weight especially fat reserves when undergoing fertility treatment. Increase your intake of healthy fats. Do not restrict calories. The above said are very important for proper functioning of your reproductive harmones which intrun is important for your treatment success.

Another interesting information to ponder : In certain regions of south India, daughter-in-law who enters husband's home for the first time, after marriage, is given cow's colostrum. Perhaps a nice way of preparing her to carry their generation :) Milk is know to increase IGF-1 levels. When I say this I do not want to make IGF-1 master of all reproductive functions, just a note because I am talking about IGF-1 in this post. Our ancestors do have lots of wisdom :)

Stupid me ! Dr said –don’t beat yourself up! He asked me to read ‘Shoulda, Woulda, Coulda’ :). I will try not to regret. Hopefully G-CSF works and perhaps everything happened for my good :) Otherwise I will not have had a chance to use G-CSF which is supposed to increase pregnancy rates atleast in a couple of studies :)


  1. Hey manju,
    A great scientific mommy is on her way...congrats, the info and the way you have written is amazing dear....ur personal life is a big stimulator for ur professional learning too and so interdependent and I am really happy for that....

  2. Devi, you always have nice things to say. I really cried reading your comment. THANKS :) It does mean a lot at this moment.

  3. You really make it seem so easy with your presentation
    but I find this matter to be actually something that I think I would never understand.
    It seems too complex and very broad for me. I'm looking forward for your next post, I'll try to get the hang of
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  4. It's funny that you came to this conclusion based on evolutionary biology, because I've suspected this as well, myself. Offspring born in famine would likely be a waste of resources, given that they would have a substantially higher probability of perishing, so adaptations and traits that would inhibit pregnancy in famine would be subject to positive selective pressure.

    But a body's autonomic system doesn't have any "perspective" that you are intentionally trying to lose weight, thus it "assumes" that a sustained famine is underway if you are continuously, dramatically losing weight. I'm glad that you brought this up, since my wife is currently losing weight in preparation for our next cycle.

    Keep up the good posts :-)

  5. Thanks : ) It is wonderful being biologists or ?

    She can loose weight but by proper excercise and by consuming healthy foods in necessary amount. If she tries to loose weight drastically (like I did !) by cutting down calories and by avoiding carbs (the major energy source ) I am sure her body will assume that there is food shortage and will try to switch off the reproductive function.

    Lots of good luck for the upcoming IVF cycle !


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  7. WOW! I'm glad I've decided to go through all your past posts as I just recently came across your blog. I had read your other post "What does science say about..." and thought, hmmmm, calorie restrictions sounds like a, well, sound choice. I guess I totally interpreted it wrong! You may have spared me from making a huge mistake. I'm about to start IVF and was going to do calorie restriction to help with egg quality. I guess there is no "quick fix" is there?

    1. Chris, it is very true that there is no 'quick fix' for egg quality. Age matters the most ! Calorie restriction when started at earlier reproductive age might help in extending the reproductive period by extending egg quality but I don't think it helps during later years. Lots of good luck Chris !


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